Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study

Abstract

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Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP–EBMT analysis

“…7 Degree of minimal residual disease (MRD) after induction chemotherapy has been identified as an independent prognostic factor of outcome in childhood ALL and some reports showed that the prognostic value of MRD might overcome that of other biological and clinical variables with widely recognized predictive significance. 8,9 Owing to its strong predictive value, MRD is being used as a tool for risk stratification in most ALL treatment protocols for both children and adults. [10][11][12] Different techniques are available for monitoring MRD, based either on PCR or multiparametric flow cytometry (MFC).…”

Flow cytometric detection of minimal residual disease in B-lineage acute lymphoblastic leukemia by using “MRD lite” panel

“…Prospective studies in large series of patients have demonstrated a strong correlation between MRD levels during clinical remission and treatment outcome. 10,11 For MRD studies, leukemia-associated immunophenotypes (LAIP)…”

“…Prospective studies in large series of patients have demonstrated a strong correlation between MRD levels during clinical remission and treatment outcome. 10,11 For MRD studies, leukemia-associated immunophenotypes (LAIP) Methods: Fifteen cases of B-ALL were studied for MRD at Day 19 of remission-induction therapy by employing a simplified MRD detection protocol using a 3-color fluorochrome conjugated antibody panel (CD19, CD10, and CD34) on bone marrow aspirate samples.…”

Prognostic impact of IKZF1 deletions in association with vincristine–dexamethasone pulses during maintenance treatment of childhood acute lymphoblastic leukemia on trial ALL-BFM 95

“…If we look at the relapse pattern of patients from ALL-BFM 2000 with the available MRD data but stratified according to the ALL-BFM 95 criteria, we observe a similar relapse cascade for these "ALL-BFM 95 IR patients" who would have been stratified to HR on ALL-BFM 2000 according to their MRD levels. 10 As treatment approaches between the ALL-BFM 95 IR and EORTC 58951 AR groups were comparable, this suggests that the stratification strategy on trial EORTC 58951 was more effective in preventing early relapsesprobably through exclusion of patients with MRD levels of ⩾ 10 − 2 after induction to the HR group.…”

“…To get an estimate on the percentage of patients, which would have been excluded from the IR group when MRD-PCR analyses would have been conducted, we applied the ALL-BFM 95 stratification criteria to patients from trial ALL-BFM 2000, which used DNA-PCR-based MRD analyses for stratification. 4,10 Of 2386 ALL-BFM 2000 patients fulfilling the ALL-BFM 95 IR stratification criteria and having the MRD data available, only 159 (6.7%) would have been stratified into the HR group according to the level of ⩾ 10 − 2 as applied in the EORTC 58951 trial (Supplementary Table 4), which could have added to the differences observed between the two studies. One additional indicator for differences in patient populations could be the fact that the relapse cascade on ALL-BFM 95 started already during maintenance treatment, while on EORTC 58951 the majority of relapses was observed after cessation of treatment.…”